This study examined the familial transmission of anxiety disorders and substance abuse using a combination of the family study/longitudinal high risk paradigms. This study also investigated comorbidity between physical disorders and mood and anxiety disorders. The chief findings reveal specificity of familial aggregation of anxiety disorders in general and the panic and social phobia subtypes in particular. Likewise, there was familial aggregation of substance abuse, with some suggestion of specificity of specific drugs. In contrast, although there was no evidence for vertical transmission of nicotine dependence, there was an increased risk of nicotine dependence among siblings. With respect to physical disorders, it was found that anxiety disorders were most strongly associated with physical disorders in general, and that there was evidence for co-transmission of migraine with anxiety and mood disorders in families. A 10-year prospective study of the offspring of parents with these conditions was conducted in order to identify the early signs and manifestations of parental disorders. A comprehensive domain of assessments of individual, familial and social risk factors among the offspring of affected and control parents was employed. The results reveal that there was specificity of expression of anxiety disorders in youth; by contrast, behavior disorders were more strongly associated with parental psychopathology and disrupted home environments in general than with specific parental disorders. Numerous abnormalities in the indirect measures of brain functioning also discriminated between offspring of parents with anxiety disorders and substance abuse, as well as children with attention deficit disorder. These findings are consistent with a congenital/developmental basis for their vulnerability to these conditions. Data collection of this study was completed at Yale University before the Principal Investigator?s relocation to the NIMH. The resources of our section have been devoted to completing the analyses of this study. Analyses conducted during the past year include: familial aggregation of smoking; comorbidity and co-aggregation of migraine and affective disorders; familial aggregation and comorbidity of cannabis dependence; inverse familial association between migraine and alcohol use disorders; assortative mating for anxiety disorders and substance use disorders; mental disorders as vulnerability factors for substance use disorders in a prospective study of high risk youth; vulnerability factors for psychopathology among offspring of alcoholic parents; sex differences in the development of anxiety disorders in youth; pubertal development, age and potentiated startle; trajectories of social functioning among youths with attention deficit disorder; neurologic correlates of attention deficit disorder; and vulnerability factors for migraine in offspring of parents with migraine. These data are being used by trainees and staff in SDGE to advance their skill in the use of statistical programs and methods, as well as to gain knowledge of epidemiologic and genetic research in psychiatry and neurology. In addition, these data provide a hypothetical basis for the current studies that are now underway in our Section.